Journal
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
Volume 63, Issue 3, Pages 355-361Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e31829260d6
Keywords
beclomethasone; darunavir; ritonavir; drug interactions; adrenal function
Categories
Funding
- National Institutes of Health Clinical Center
- National Institute of Allergy and Infectious Diseases
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]
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Objective: To identify an alternative inhaled corticosteroid to fluticasone propionate that can be safely coadministered with HIV protease inhibitors, the safety and pharmacokinetics of beclomethasone dipropionate (BDP) and its active metabolite, beclomethasone 17-monopropionate (17-BMP), in combination with ritonavir (RTV) and darunavir/ritonavir (DRV/r) were assessed. Design: Open-label, prospective, randomized pharmacokinetic and pharmacodynamic study in healthy volunteers. Methods: Thirty healthy volunteers received inhaled 160 mu g bid BDP for 14 days and were then randomized (1: 1: 1) into 3 groups: group 1 (control) remained on BDP alone for 28 days, group 2 received 100 mg bid BDP + RTV for 28 days, and group 3 received 600/100 mg bid BDP + DRV/r for 28 days. Pharmacokinetic sampling for 17-BMP was performed on days 14 and 28, and pharmacokinetic parameter values were compared within patients and between groups. Cortisol stimulation testing was also performed on days 1, 14, 28, and 42 and compared within and between groups. Results: Geometric mean ratios (day 28: day 14) (90% confidence interval) for 17-BMP area under the concentration-time curve in groups 1, 2, and 3, respectively, were 0.93 (0.81 to 1.06, P = 0.27), 2.08 (1.52 to 2.65, P = 0.006), and 0.89 (0.68 to 1.09, P = 0.61). There were no significant reductions in serum cortisol levels within or between groups (P > 0.05). Conclusions: DRV/r did not increase 17-BMP exposure, whereas RTV alone produced a statistically significant but clinically inconsequential 2-fold increase in 17-BMP exposure. Adrenal suppression was not observed in any of the study groups. These data suggest that BDP can be safely coadministered with DRV/r and likely other RTV-boosted protease inhibitors.
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